Human Disease

Question 1

Mutations of transcription factor coding genes result

Answer 1

A functional TF that binds to dna but don’t activate gene expression
Haploid insufficiency (amount of protein insufficient)
Unresponsive to signals

Question 2

Mutation of co-activators

Answer 2

Lethal if no CBP is made
Disease of only one CBP functional gene
Sometimes incorrect protein-protein interactions
-removes co-activator (CBP-Huntington’s protein)

Question 3

Mutation of RNA splicing

Answer 3

Class 1: mutation that affects RNA splicing (incorrect splice variant)
Class 2: inactive splicing factor

Question 4

Therapeutic strategies for altering TF activity

Answer 4

Enhance IkB expression
Reduce NFkB expression
Inhibit phosphorylation of IkB
-by aspirin/blocking protein-protein interactions with a peptide
Drugs can block p53-MDM2 interaction

Question 5

Gene therapy

Answer 5

Designer zinc fingers link to inhibitory domains/activator domains
Delivery of synthetic gene into target cell
-eg adenovirus Cell receptor endocytosis

Question 6

siRNA limitations

Answer 6

Delivery problems
Side effects due to off-target actions
Disturbance of physiological functions of cellular machinery involved in gene silencing
Induction of innate immune response